Use of alcohol, drugs, inhalants, and smoking tobacco and the long-term risk of depression in men: A nationwide Swedish cohort study from 1969-2017.

BACKGROUND: The use of alcohol, drugs, inhalants, and smoking tobacco may lead to mood disorders such as depression. However, knowledge on the independent contributions of the use of these substances to the risk of depression is lacking. METHODS: The study cohort consisted of 24,564 men included in the Swedish national military conscription register who were conscripted in 1969-1970 and followed until 2017. Cox proportional hazard ratios were used to estimate the risk of depression according to alcohol, drug, inhalant, and cigarette consumption, and adjusted for body mass index, verbal comprehension test scores, handgrip strength, and the other main exposures investigated. RESULTS: During an average follow-up period of 44 years, 4500 men were diagnosed with or treated for depression at a mean age of 54 years. A dose-dependent association was found in men who smoked cigarettes, with the highest risk for smoking >20 cigarettes per day, at time of conscription (aHR 1.86, 95 % CI 1.61-2.16, p < 0.001). Independent associations with an increased risk of depression were found for the use of drugs at least once (aHR 1.21, 95 % CI 1.10-1.32, p < 0.001) and >50 times (aHR 1.48, 95 % CI 1.23-1.77, p < 0.001) and the use of inhalants (aHR 1.16, 95 % CI 1.05-1.29). Excessive alcohol intake was not associated with the risk of depression. CONCLUSION: The results suggest that people who reported to have used cigarettes, alcohol, or drugs at 18 years of age have a moderately increased risk of depression later in life.

Functional biodiversity of marine soft-sediment polychaetes from two Mediterranean coastal areas in relation to environmental stress.

Biological Traits Analysis (BTA) was used to identify functional features of infaunal polychaete assemblages associated with contamination in two Italian coastal areas: the harbour of Trieste (Adriatic Sea) and the Mar Piccolo of Taranto (Ionian Sea). The analysis was performed on 103 taxa, collected at four stations in each area. The two areas differed in species composition. The low diversity and the presence of stress-tolerant species in more polluted sites were not reflected in functional diversity, due to species contributing little to community functions or being functionally redundant. Sand and clay fractions were significant drivers of trait category expressions, however other environmental parameters (depth, total organic carbon and nitrogen, and Hg in sediments) influenced traits composition. Motile was the prevalent trait in environments with coarse sediments, and tube-builder were related to fine-grained ones. Motile, endobenthic and burrower were essential traits for living in contaminated sediments. Epibenthic and sessile polychaetes dominated at stations subjected to high organic loads. BTA offers an integrative approach to detect functional adaptations to contaminated sediments and multiple anthropogenic stressors.

Th17 Pathway As a Target for Multipotent Stromal Cell Therapy in Dogs: Implications for Translational Research.

Detrimental Th17 driven inflammatory and autoimmune disease such as Crohn's disease, graft versus host disease and multiple sclerosis remain a significant cause of morbidity and mortality worldwide. Multipotent stromal/stem cell (MSC) inhibit Th17 polarization and activation in vitro and in rodent models. As such, MSC based therapeutic approaches are being investigated as novel therapeutic approaches to treat Th17 driven diseases in humans. The significance of naturally occurring diseases in dogs is increasingly recognized as a realistic platform to conduct pre-clinical testing of novel therapeutics. Full characterization of Th17 cells in dogs has not been completed. We have developed and validated a flow-cytometric method to detect Th17 cells in canine blood. We further demonstrate that Th17 and other IL17 producing cells are present in tissues of dogs with naturally occurring chronic inflammatory diseases. Finally, we have determined the kinetics of a canine specific Th17 polarization in vitro and demonstrate that canine MSC inhibit Th17 polarization in vitro, in a PGE2 independent mechanism. Our findings provide fundamental research tools and suggest that naturally occurring diseases in dogs, such as inflammatory bowel disease, may be harnessed to translate novel MSC based therapeutic strategies that target the Th17 pathway.

Evaluation of the presence of intraluminal cancer cells following rectal washout in rectal cancer surgery.

BACKGROUND: The presence of intraluminal tumour cells in colorectal cancer is known, as is their ability to implant in colorectal anastomoses, causing perianastomotic tumour growth. There is no consensus as to the volume and agent to use for rectal washout. The purpose of this study was to assess the efficacy of our current routine for rectal washout in eliminating intraluminal tumour cells. METHODS: Sixty consecutive patients undergoing low anterior resection or low Hartmann's procedure for rectal cancer at our unit were included. After the pelvic dissection was completed, the bowel was cross-clamped distal to the tumour and the prewashout sample (no. 1), was obtained by instilling 50 ml of saline and collecting the return fluid. A rectal washout followed using 500 ml of sterile water, 2 × 500 ml of 70 % ethanol and 500 ml of sterile water (sample no. 2-4) and the postwashout sample (no. 5) was obtained by using 50 ml of saline. The samples were examined and categorized as non-malignant or malignant at the Department of Pathology. The usual pathology report information was also assessed. RESULTS: In 33 of the 60 patients, cancer cells were identified in the prewashout sample. The rectal washout eliminated intraluminal cancer cells in 30 of the 33 patients. All of the remaining 3 had a higher blood loss (p = 0.026) and a tendency towards more polypoidal tumours (p = 0.053). CONCLUSIONS: A rectal washout volume larger than 2,000 ml might be necessary to eliminate all intraluminal tumour cells in total mesorectal excision for rectal cancer.

Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study.

BACKGROUND: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. RESULTS: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. CONCLUSIONS: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov. identifier NCT01502982.

Circadian modulation of neuroplasticity in humans and potential therapeutic implications.

Learning, memory, and recovery from various neurological insults occur by a process known as neuroplasticity. Neuroplastic changes occur by a variety of physiological processes that modify central nervous system structure and function. The ability to non-invasively induce neuroplastic change in humans is developing as an exciting new field in neuroscience and may ultimately improve treatment outcomes for those suffering various neurological conditions reliant on neuroplasticity for recovery of function. The induction of neuroplastic changes is influenced by several factors, and do not occur evenly throughout the day, but appear to be under circadian control. This review will discuss the known mechanisms and techniques used to induce neuroplasticity, circadian modulation of neuroplasticity, and will discuss the potential implications of these findings for human neurorehabilitation.

Pallidotomy does not ameliorate abnormal intracortical inhibition in Parkinson's disease.

Motor cortex excitability was assessed in 12 patients with Parkinson's disease (PD) using transcranial magnetic stimulation. Patients were studied when mobile and medicated ("ON") and when immobile after medication withdrawal ("OFF"). Results were compared to eight age-matched and 11 young controls. Cortical excitability was assessed by measurement of resting motor threshold (RMT), intracortical inhibition and cortical silent period duration. In five patients, the studies included assessments following pallidotomy. Cortical excitability was abnormal in patients with PD with reduced RMT in "ON" and "OFF" states, and less effective intracortical inhibition. Pallidotomy did not affect cortical excitability in either "ON" or "OFF" states, indicating that enhanced motor cortex excitability in patients with PD is unaffected by pallidotomy despite clinical improvement in motor scores.

The life circumstances of persons with a psychiatric disability: a survey in a region in southern Sweden.

This article describes the life circumstances of persons with a psychiatric disability living in one urban and six rural areas in a single region in Sweden. Furthermore, the life circumstances of persons with a psychiatric disability are discussed in relation to the aims of social policies in Sweden. Data were collected by means of a survey study exploring the formal support provided by local authorities to its citizens and the informal support given by family members and volunteers. The results reveal how the respondents themselves describe their life circumstances in terms of their living conditions, occupation and activities, health, and formal and informal support. The results indicate that persons with a psychiatric disability, regardless of where they live, need both formal and informal support in order to cope with their everyday lives. The family plays an important role in this, and it is essential for the formal and informal support systems to cooperate with each other. The lack of activities and opportunities for work experienced by persons with a psychiatric disability indicates that the sociopolitical goal of fostering access to employment and work and to earning a living for this group is far from having been attained.

Places, social relations and activities in the everyday lives of older adults with psychiatric disabilities: an interview study.

BACKGROUND: Knowledge about the daily life of older adults with psychiatric disabilities is extremely limited, especially from the standpoint of the individual. The overall aim of this study was to describe and analyze the ways in which older adults with a psychiatric disability experience places, social relations and activities in different arenas of their everyday lives. METHOD: Twelve older adults (>55 years) with a psychiatric disability were interviewed either once or twice, using different interview techniques. The first interviews were semi-structured and the second were in-depth interviews guided by a site-map. The interview texts were analyzed using qualitative content analysis, proceeding from open to focused coding in several steps. RESULTS: Although the respondents spent most of their time in their own homes, some also spent a lot of time at day-care centers and other similar places. The amount of time spent in places in the public arena varied a great deal. The interviewees' experiences of the places, relationships and activities in their everyday lives can be related to aspects of freedom and coercion, internal and external structure, and relationships and support. CONCLUSION: The provision of a varied range of services and support in diverse settings in order to make these accessible to persons of different ages and needs is an important challenge for welfare politics.

Adherence to treatment in Swedish HIV-infected patients.

OBJECTIVES: The objectives were to assess the prevalence of adherence to antiretroviral treatment in Swedish human immunodeficiency virus (HIV)-infected patients and to evaluate factors associated with adherence. METHODS: All HIV-treated patients, who attended one of 30 (of a total of 32) Swedish infectious diseases clinics, during 7 months, were asked to complete an anonymous questionnaire containing the 9-item Morisky Medication Adherence Scale (MMAS) and questions about other factors potentially affecting adherence. The summary score of MMAS ranges from 1 to 13, where 13 indicates perfect adherence; patients scoring 11 or above (corresponding to 95% adherence level) were classified as 'adherent'. RESULTS AND DISCUSSION: In total 946 patients participated (response rate 97.5%). The proportion of patients who reported not missing a dose during the day prior to the completion of the questionnaire was 97% and the proportion classified as 'adherent' was 63%. 'Adherent' patients were more likely to have a good relationship with their health care professionals (P < 0.05) and not have problems with drugs or alcohol (P < 0.01). Being older (P < 0.01) and having a shorter time on current treatment (P < 0.01) and on treatment in total (P < 0.05) were factors also associated with good adherence. CONCLUSION: Factors modifiable for interventions by health care professionals are patient-provider relationship, drug or alcohol problems and patients with long treatment periods.

Highly sensitive polymer-based cantilever-sensors for DNA detection.

We present a technology for the fabrication of cantilever arrays aimed to develop an integrated biosensor microsystem. The fabrication process is based on spin coating of the photosensitive polymer and near-ultraviolet exposure. Arrays of up to 33 microcantilevers are fabricated in the novel polymer material SU-8. The low Young's modulus of the polymer, 40 times lower than that of silicon, enables to improve the sensitivity of the sensor device for target detection. The mechanical properties of SU-8 cantilevers, such as spring constant, resonant frequency and quality factor are characterized as a function of the dimensions and the medium. The devices have been tested for measurement of the adsorption of single stranded DNA and subsequent interstitial adsorption of lateral spacer molecules. We demonstrate that sensitivity is enhanced by a factor of six compared to that of commercial silicon nitride cantilevers.

Stretch reflexes in the human masticatory muscles: a brief review and a new functional role.

Stretch reflexes play a vital role in fine-tuning movements and in automatically maintaining posture. This article briefly reviews the operation of the stretch reflex in the human masticatory system. The conventional approach of stretching muscles in an open-loop manner has yielded much valuable information on the operation of this reflex. In particular, it has revealed that stretching the jaw-closing muscles evokes a reflex response with two major components. The short-latency reflex is favoured when stretches are brisk, but slower stretches evoke an additional long-latency component. In the hand muscles, the long-latency response is transcortical: in the masticatory muscles, it is not. In addition to its role in servo-control of muscle length during chewing, the stretch reflex in the jaw-closing muscles maintains the vertical position of the mandible during vigorous head movements such as those that occur during running, jumping, hopping and other vigorous whole-body movements in which the head moves briskly up and down. This is an interesting model system in which to investigate stretch reflexes with natural stimuli under unrestrained, physiological conditions.

A double-blind placebo-controlled study of the effects of amphetamine and physiotherapy after stroke.

Major therapeutic advances in the rehabilitation of subacute stroke are lacking. One promising approach is treatment with amphetamine in combination with physiotherapy so as to promote motor function. In a randomized, double-blind, placebo-controlled clinical trial, the effect of 10 sessions with 10 mg of amphetamine combined with physiotherapy during a 5-week period was investigated in 39 geriatric patients who had been admitted to a stroke rehabilitation unit. Motor function (Fugl-Meyer motor performance score) and activities of daily living (ADL; Barthel's index) were assessed at baseline and at the end of treatment. All patients improved significantly over the intervention period. Amphetamine-treated patients did not show any increase in motor function or ADL as compared to the control group. Rehabilitation with amphetamine at this dosage and interval, combined with physiotherapy, did not promote motor recovery or functional capacity in patients suffering from stroke.

Asymmetry of motor cortex excitability during a simple motor task: relationships with handedness and manual performance.

Transcranial magnetic stimulation (TMS) was used to assess the relative contribution of the corticospinal (CS) pathway in activating the first dorsal interosseous (FDI) muscle in each hand of 16 right- (RH) and 16 left-handed (LH) subjects with varied degrees of hand preference. It was hypothesised that asymmetry in corticospinal activation of the two hands may be related to hand preference and interlimb differences in manual performance. Subjects performed isometric index finger abduction at force levels of 0.5 N, 1 N and 2 N while TMS was applied at resting threshold intensity (T), 0.9T, or 0.8T. The amount of contraction-induced facilitation of the muscle evoked potential (MEP) was used as an estimate of corticospinal involvement in the task. Patterns of MEP facilitation in each hand were compared with measures of manual performance (finger tapping speed, Purdue pegboard, maximal FDI strength). Threshold TMS intensities for an MEP in FDI at rest were similar in LH and RH subjects, and did not vary between hands. Facilitation of the MEP with voluntary activation was larger overall on the left side (P<0.05), but the asymmetry was dependent on the degree of lateralisation of hand preference. For subjects with consistent hand preference (either LH or RH), MEP facilitation in active FDI was larger for the left hand. For non-consistent RH subjects, contraction-induced MEP facilitation was larger in the right FDI muscle than the left. Asymmetry of MEP facilitation was not correlated with differences between hands in finger tapping speed or performance in the pegboard task, but was associated with relative differences in FDI strength. MEP facilitation tended to be larger in the stronger FDI muscle of the pair. We conclude that corticospinal involvement in the command for index finger abduction is generally greater when the left hand is used, although in RH subjects the asymmetry is influenced by the degree of lateralisation of hand preference. The corticospinal asymmetry is not related to speed or dexterity of finger movements, but the association with muscle strength suggests that it may be influenced in part by preferential use of one hand for tasks which strengthen the FDI muscle.

Task-dependent control of human masseter muscles from ipsilateral and contralateral motor cortex.

Corticotrigeminal projections to human masseter motoneuron pools were investigated with focal transcranial magnetic stimulation (TMS). Responses in left and right masseter muscles were quantified from the surface electromyogram (EMG) during different biting tasks. During bilateral biting, TMS elicited motor evoked potentials (MEPs) in both masseter muscles. On average, the MEP area in the masseter contralateral to the stimulus was 39% larger than in the ipsilateral muscle, despite comparable pre-stimulus EMG in both muscles. MEPs elicited while subjects attempted unilateral activation of one masseter muscle were compared with those obtained in the same muscle during a bilateral bite at an equivalent EMG level. MEPs in the masseter contralateral to the stimulated hemisphere were significantly smaller during unilateral compared with bilateral biting. There was no significant difference in the size of ipsilateral MEPs during ipsilateral and bilateral biting. We conclude that the corticotrigeminal projections to masseter are bilateral, with a stronger contralateral projection. The command for unilateral biting is associated with a reduced excitability of corticotrigeminal neurons in the contralateral, but not the ipsilateral motor cortex. We suggest that this may be accomplished by reduced activity of a population of corticotrigeminal neurons which branch to innervate both masseter motoneuron pools.

The prevalence of violence investigated in a pregnant population in Sweden.

All women registered for antenatal care within a Swedish municipality during a 6-month period were assessed regarding acts of violence. The Abuse Assessment Screen was used on two occasions during pregnancy, and once between 4 and 20 weeks after delivery. The efficacy of repeated interviews was investigated, and characteristics of abused and non-abused women were compared. The participation rate was 93% (1038 women). Physical abuse by a close acquaintance or relative during or shortly after pregnancy was reported by 1.3%, and by 2.8% when the year preceding pregnancy was included. The lifetime prevalence of emotional, physical or sexual abuse was 19.4%. Repeated questioning increased the detection of abuse. Women abused during pregnancy reported more preceding ill-health and more elective abortions than non-abused women. Intervention against sexual violence has been on the political agenda in Sweden for several decades. Even so, physical abuse is a risk factor comparable in frequency to obstetric complications such as gestational diabetes and pre-eclampsia. Routines need to be established to make questioning about violence an integral part of the standardized screening for risk factors during pregnancy.

Reliability and reproducibility of brain tissue volumetry from segmented MR scans.

Reliable measurement of different tissue volumes in the living brain is of great importance for human brain research. In this article, we report on the inter- and intraoperator reliability and scan-rescan reproducibility of segmented intracranial tissue volumes from MR images using the image analysis software suite BRAINS. The absolute data of tissue volume measurements are also presented. The reliability and consistency of the measurements of the segmented volumes were excellent. The segmentation is robust and rapid and the volume measurements are plausible and suitable for quantitative studies in clinical brain research.

Factors associated with pregnancy termination in Ukrainian women.

OBJECTIVES: To study differences in social and demographic characteristics between women undergoing an induced abortion and antenatal care attendants in the Ukraine. DESIGN: Hospital-based unmatched case control study. METHODS: From a survey including 1,694 women of fertile age, who attended five women's clinics in the Donetsk region, Ukraine, we studied those who came for termination of pregnancy (n = 919) and for antenatal care (n = 478). The data were obtained through an anonymous self-questionnaire. From the 192-item questionnaire questions dealing with social and demographic characteristics, previous pregnancy experience, and attitude towards abortion were analyzed. Multiple logistic regression was used to analyze the risk of pregnancy termination. RESULTS: Termination of pregnancy was associated with being single (OR = 11.8). Both previous childbirth and previous induced abortion were other determinants as well as being younger than 19 years old (OR = 3.8), having a positive attitude towards abortion (OR = 2.7), and sharing apartment with parents (OR = 1.9). A higher risk for an induced abortion was found among women with a history of previous induced abortion(s). Neither income nor educational level was identified as a risk factor for pregnancy termination. CONCLUSION: This study demonstrated major social and demographic differences between women attending for abortion and antenatal care patients, and highlights some of the factors influencing the decision to terminate a pregnancy.

Combined oral contraceptives do not increase the risk of back and pelvic pain during pregnancy or after delivery.

OBJECTIVES: To elucidate whether the duration of previous use of combined oral contraceptives (COC) is associated with disabling back or pelvic pain during pregnancy and pain persisting eight months after delivery. METHODS: Questionnaires were distributed to a group of women at 36 weeks of pregnancy and eight months after their delivery. There were no exclusion criteria. Disabling pain was defined as moderate or severe pain restricting physical activity. Multiple logistic regression analysis of disabling pain during pregnancy and persistent pain after delivery comprised the duration of COC use adjusted for age, pain in a previous pregnancy and a history of back pain when not pregnant. RESULTS: The study comprised 161 women. Pain during pregnancy was classified as disabling in 57 of the women (35%), pain in a previous pregnancy being a risk factor, odds ratio (OR) 5.0 (95% CI 2.1; 12.1), whereas no association was found with the duration of COC use. Persistent pain eight months after delivery was reported by 41 women (26%), risk factors being a history of back pain when not pregnant; OR 7.5 (2.8; 19.5), disabling pain in the recent pregnancy; OR 5.0 (1.9; 13.4), and short use of COC; 0-<1 year; OR 4.2 (1.3; 12.9), 1-<5 years; OR 4.6 (1.5; 14.4) (reference=>10 years). CONCLUSION: The results indicate that non- or short term users of COC have an increased risk of persistent pain after delivery compared to long term users. No association was found between the duration of COC use and back or pelvic pain during pregnancy.

Reduced interhemispheric inhibition in musicians.

In vivo magnetic resonance imaging has revealed that the anterior half of the corpus callosum is larger in musicians trained intensively from an early age than in untrained subjects. The corpus callosum is crucial for the coordination of bimanual motor activity, but neurophysiological correlates of morphological differences in the corpus callosum of musicians are not known. In the present study we have used transcranial magnetic stimulation (TMS) to assess interhemispheric inhibition in six adult professional musicians who began musical training at an early age. Conditioning TMS was applied to the hand area of the motor cortex of one hemisphere, followed 4-16 ms later by a test stimulus applied to the other hemisphere. Tests were performed at rest, and with the first dorsal interosseous muscle contralateral to the conditioning hemisphere voluntarily active. Conditioning TMS in musicians was 29% less effective at reducing the size of the test MEP at rest, and 63% less effective in the active condition, compared with control subjects. We conclude that transcallosal interhemispheric inhibitory circuits activated by TMS are less effective in musicians than in controls.